A natural history study of autosomal dominant GUCY2D-associated cone-rod dystrophy.

IF 2.6 4区医学 Q2 OPHTHALMOLOGY

Documenta Ophthalmologica Pub Date : 2023-12-01 Epub Date: 2023-09-29 DOI:10.1007/s10633-023-09954-7

Amanda J Scopelliti, Robyn V Jamieson, Elizabeth H Barnes, Benjamin Nash, Sulekha Rajagopalan, Elisa L Cornish, John R Grigg

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Abstract

Purpose: To describe the natural history of autosomal dominant (AD) GUCY2D-associated cone-rod dystrophies (CRDs), and evaluate associated structural and functional biomarkers.

Methods: Retrospective analysis was conducted on 16 patients with AD GUCY2D-CRDs across two sites. Assessments included central macular thickness (CMT) and length of disruption to the ellipsoid zone (EZ) via optical coherence tomography (OCT), electroretinography (ERG) parameters, best corrected visual acuity (BCVA), and fundus autofluorescence (FAF).

Results: At first visit, with a mean age of 30 years (range 5-70 years), 12 patients had a BCVA below Australian driving standard (LogMAR ≥ 0.3 bilaterally), and 1 patient was legally blind (LogMAR ≥ 1). Longitudinal analysis demonstrated a deterioration of LogMAR by - 0.019 per year (p < 0.001). This accompanied a reduction in CMT of - 1.4 µm per year (p < 0.0001), lengthened EZ disruption by 42 µm per year (p = < 0.0001) and increased area of FAF by 0.05 mm² per year (p = 0.027). Similarly, cone function decreased with increasing age, as demonstrated by decreasing b-wave amplitude of the light-adapted 30 Hz flicker and fused flicker (p = 0.005 and p = 0.018, respectively). Reduction in CMT and increased EZ disruption on OCT were associated with functional changes including poorer BCVA and decreased cone function on ERG.

Conclusion: We have described the natural long-term decline in vision and cone function associated with mutations in GUCY2D and identified a set of functional and structural biomarkers that may be useful as outcome parameters for future therapeutic clinical trials.

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常染色体显性遗传GUCY2D相关锥杆营养不良的自然史研究。

目的：描述常染色体显性遗传（AD）GUCY2D相关锥杆营养不良（CRDs）的自然史，并评估相关的结构和功能生物标志物。方法：对两个部位的16例AD GUCY2D CRD患者进行回顾性分析。评估包括通过光学相干断层扫描（OCT）、视网膜电图（ERG）参数、最佳矫正视力（BCVA）和眼底自发荧光（FAF）进行的中央黄斑厚度（CMT）和椭球区破坏长度（EZ）。结果：首次就诊时，平均年龄为30岁（5-70岁），12名患者的BCVA低于澳大利亚驾驶标准（LogMAR ≥ 双侧0.3），1名患者为合法盲人（LogMAR ≥ 1）。纵向分析显示LogMAR每年恶化-0.019（p 每年2次（p = 0.027）。类似地，锥函数随着年龄的增加而降低，如适应光的30Hz闪烁和融合闪烁的b波振幅降低所示（p = 0.005和p = 0.018）。OCT上CMT的减少和EZ破坏的增加与功能变化有关，包括BCVA较差和ERG上锥体功能下降。结论：我们已经描述了与GUCY2D突变相关的视觉和锥体功能的自然长期下降，并确定了一组功能和结构生物标志物，这些生物标志物可能作为未来治疗的结果参数临床试验。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Documenta Ophthalmologica 医学-眼科学

CiteScore

3.50

自引率

21.40%

发文量

审稿时长

>12 weeks

期刊介绍： Documenta Ophthalmologica is an official publication of the International Society for Clinical Electrophysiology of Vision. The purpose of the journal is to promote the understanding and application of clinical electrophysiology of vision. Documenta Ophthalmologica will publish reviews, research articles, technical notes, brief reports and case studies which inform the readers about basic and clinical sciences related to visual electrodiagnosis and means to improve diagnosis and clinical management of patients using visual electrophysiology. Studies may involve animals or humans. In either case appropriate care must be taken to follow the Declaration of Helsinki for human subject or appropriate humane standards of animal care (e.g., the ARVO standards on Animal Care and Use).